This proposal builds upon our proven track record of productivity as an established Center of Excellence within the NIGMS Modeling of Infectious Disease Agent Study program. To date, our Center of Excellence has prepared and published 174 manuscripts in peer-reviewed journals; hosted five major trans-disciplinary conferences; introduced 95 diverse students to research and training opportunities in computational modeling; developed ten innovative computational methods, tools or platforms; and provided valuable, timely decision support to health officials at the county (Allegheny), state (Pennsylvania), national (CDC, ASPR, BARDA), and international (WHO) levels. The PI at Pittsburgh and the senior investigators at key partnering institutions (Carnegie Mellon, Johns Hopkins, and Imperial) form an established team of experienced modelers who are proven to be highly collaborative with each other and with colleagues across the entire MIDAS network. The Center of Excellence research plan consists of five interacting research projects which focus on (1) Data and Parameters; (2) Behavioral Dynamics; (3) Evolutionary Dynamics; (4) Models and Forecasts; and (5) Policy Methods. All five projects are linked to each other as steps along a public health decision-support metamodel of information flow. The five research projects are led by outstanding research academicians who are highly expert in their respective areas. Expected research project pay-offs include deeper mechanistic understanding of epidemic dynamics, increased accuracy of epidemic forecasting, and improved methods to assess the value of information required for greater confidence in public health decision-making. The Center of Excellence also houses four supporting components, on Policy Studies; Software and Computing; Training, Outreach, and Diversity; and Administration. Each supporting component is led by an exceptionally well-qualified expert and is designed to interact with and facilitate the work of the research projects. A unique feature of this Center of Excellence is its remarkably interdisciplinary character, with vigorous participation by physicians, epidemiologists, behavioral scientists, microbial geneticists, computer scientists, health policy experts, lawyers, and public health practitioners. We are well positioned to provide continued leadership in the renewed MIDAS network, and we are deeply committed to collaborative research not only within our own Center Excellence but across the entire MIDAS network structure.